Abstract

1940

We have generated a spontaneous pancreatic tumor model in transgenic mouse where T-antigen and firefly luciferase expression is driven by the elastase I promoter in the acinar cells of the pancreas (EL1-luc/EL1-SV40 T-antigen transgenic mouse). Development of pancreatic tumor lesions in this model can be monitored non-invasively through imaging and quantifying light emission which is proportional to the total luciferase expression, which, in turn, is proportional to the tumor burden. The transgenic mice showed pancreas specific expression of luciferase activity. The bioluminescence signal was at a detectable basal level and was steady until tumor started to develop. The latency of tumor development varied from 13 weeks to more than 20 week. Development of the primary tumors in the pancreatic tissue was accompanied by metastatic lesions in the abdominal organs, including adipose tissues, liver and kidney. We tested the effect of rapamycin on tumor development. Mice were imaged biweekly using an IVIS to monitor the luciferase signal from the pancreatic region during treatment. In both male and female transgenic mice, we observed significant suppression of luciferase induction in the pancreas. The optical imaging data correlated with reduction in tumor occurrence rate in the rapamycin treated mice as compared to the placebo treated controls, as determined by necropsy performed by the end of the study. Thus the EL1-luc/EL1-SV40 T-antigen transgenic mouse model provides a non-invasive approach for monitoring the pancreatic tumor development process and offers a convenient tool for evaluation of novel therapeutics against pancreatic cancer. Tumor growth suppression through inhibition of the mTOR pathway further validates this model as clinically relevant.